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This study estimated the effect of Holstein-Friesian, Brown Swiss, Jersey, Simmental and Alpine Grey cattle breeds on milk mineral contents (Ca, Mg, P, K, and Na) in multibreed herds using data predicted with mid-infrared spectroscopy. The dataset included 139,821 observations from 16,566 cows and 977 herds. Fixed effects considered in the mixed model were breed, parity, stage of lactation and first-order interactions, and random effects were cow, herd-test-date, and the residual. Multiple comparisons of least squares means were performed for the main effect of breed, parity, and stage of lactation using Bonferroni adjustment. Holstein-Friesian yielded milk with the lowest fat, protein, and casein concentration, and Ca, Mg, and P contents, whereas Jersey cows produced milk with the greatest fat, protein, and casein concentration, and Ca and Mg contents. Results of this study suggest that mixing milk from different breeds could enhance milk composition and technological ability, and therefore contribute to improve dairy industry efficiency., (© 2018 Japanese Society of Animal Science.)

In this study, an in vitro antileishmanial assessment of plant extracts from 12 genera and 46 species growing in Cuba belonging to Solanaceae family was performed. A total of 226 extracts were screened against promastigotes of Leishmania amazonensis, and cytotoxicity of active extracts [median inhibitory concentration (IC 50 ) promastigotes <100 µg/mL] was determined on peritoneal macrophage from BALB/c mice. Extracts that showed selective index >5 were then assayed against intracellular amastigote. Metabolomics analysis of promissory extracts was performed using chemical profile obtained by ultra performance liquid chromatography. Only 11 extracts (4.9%) from nine plants were selected as potentially actives: Brunfelsia cestroides A. Rich, Capsicum annuum L., Capsicum chinense Jacq., Cestrum nocturnum L., Nicotiana plumbaginifolia Viv., Solanum havanense Jacq., Solanum myriacanthum Dunal, Solanum nudum Dunal and Solanum seaforthianum And., with IC 50  < 50 µg/mL and selectivity index >5. Metabolomics analysis demonstrated significant differences in the chemical profiles with an average of 42.8 (range 31-88) compounds from m/z 104 to 1477, which demonstrated the complex mixture of compounds. In addition, no common markers among active extracts were identified. The results demonstrate the importance of the Solanaceae family to search new antileishmanial agents, particularly in unexplored species of this family. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background and Purpose: Presynaptic, release-regulating metabotropic glutamate 2 and 3 (mGlu2/3) autoreceptors exist in the CNS. They represent suitable targets for therapeutic approaches to central diseases that are typified by hyperglutamatergicity. The availability of specific ligands able to differentiate between mGlu2 and mGlu3 subunits allows us to further characterize these autoreceptors. In this study we investigated the pharmacological profile of mGlu2/3 receptors in selected CNS regions and evaluated their functions in mice with experimental autoimmune encephalomyelitis (EAE)., Experimental Approach: The comparative analysis of presynaptic mGlu2/3 autoreceptors was performed by determining the effect of selective mGlu2/3 receptor agonist(s) and antagonist(s) on the release of [(3)H]-D-aspartate from cortical and spinal cord synaptosomes in superfusion. In EAE mice, mGlu2/3 autoreceptor-mediated release functions were investigated and effects of in vivo LY379268 administration on impaired glutamate release examined ex vivo., Key Results: Western blot analysis and confocal microscopy confirmed the presence of presynaptic mGlu2/3 receptor proteins. Cortical synaptosomes possessed LY541850-sensitive, NAAG-insensitive autoreceptors having low affinity for LY379268, while LY541850-insensitive, NAAG-sensitive autoreceptors with high affinity for LY379268 existed in spinal cord terminals. In EAE mice, mGlu2/3 autoreceptors completely lost their inhibitory activity in cortical, but not in spinal cord synaptosomes. In vivo LY379268 administration restored the glutamate exocytosis capability in spinal cord but not in cortical terminals in EAE mice., Conclusions and Implications: We propose the existence of mGlu2-preferring and mGlu3-preferring autoreceptors in mouse cortex and spinal cord respectively. The mGlu3 -preferring autoreceptors could represent a target for new pharmacological approaches for treating demyelinating diseases., (© 2016 The British Pharmacological Society.)

Objective: To evaluate whether Baby-guard-a new medical device with an ergonomic 3-chamber inflatable abdominal belt-can reduce complications associated with vaginal delivery., Methods: A randomized controlled single-blind prospective study of 80 pregnant women delivering at term was conducted at San Giuseppe Hospital, Empoli, Italy. In the study group (n=40), the abdominal belt was inflated to optimal therapeutic pressures. In the control group (n=40), the abdominal belt was inflated to minimal, non-therapeutic pressures. Factors relating to maternal, fetal, and labor complications during vaginal delivery were evaluated., Results: Compared with the control group, women in the study group experienced a lower incidence of perineal and cervical lacerations (P<0.001); reduced use of the Kristeller maneuver (P<0.001); shorter duration of the second stage of labor (P<0.001); less psychologic and physical fatigue (P<0.001); fewer maternal requests for cesarean delivery during labor (P<0.001); fewer vacuum extractions (P<0.01); and fewer cesarean deliveries (P<0.02). No neonatal intensive care unit admissions were recorded in the study group versus 7 in the control group (P<0.012)., Conclusion: Use of the ergonomic 3-chamber inflatable abdominal belt system reduced the incidence of risks associated with vaginal labor. Clinical trials.gov identifier: NCT01566331., (Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

We present the new release of the ORAC engine (Procacci et al., Comput Chem 1997, 18, 1834), a FORTRAN suite to simulate complex biosystems at the atomistic level. The previous release of the ORAC code included multiple time steps integration, smooth particle mesh Ewald method, constant pressure and constant temperature simulations. The present release has been supplemented with the most advanced techniques for enhanced sampling in atomistic systems including replica exchange with solute tempering, metadynamics and steered molecular dynamics. All these computational technologies have been implemented for parallel architectures using the standard MPI communication protocol. ORAC is an open-source program distributed free of charge under the GNU general public license (GPL) at http://www.chim.unifi.it/orac., (2009 Wiley Periodicals, Inc.)

Background and Purpose: Two metabolites of tryptophan, 5-hydroxyindole and kynurenic acid (kynurenate) affect the function of alpha7 nicotinic acetylcholine receptors (nAChRs), as measured by electrophysiological and Ca2+ fluorescence techniques. To better understand the modulations by 5-hydroxyindole and kynurenate of the function of nAChR subtypes, we compared the effects of 5-hydroxyindole and kynurenate on the release of various transmitters evoked by nAChR activation., Experimental Approach: The function of alpha7nAChRs located on glutamatergic terminals was investigated by monitoring the release of [3H]D-aspartate or of endogenous glutamate from neocortical synaptosomes. We also comparatively considered non-alpha7 release-enhancing nAChRs localized on hippocampal noradrenergic or cholinergic terminals, as well as on striatal dopaminergic terminals., Key Results: Epibatidine or nicotine, inactive on their own on basal release, enhanced [3H]D- aspartate and glutamate efflux in presence of 5-hydroxyindole. The release evoked by nicotine plus 5-hydroxyindole was abolished by methyllycaconitine or alpha-bungarotoxin. Presynaptic nAChRs mediating the release of [3H]noradrenaline ([3H]NA), [3H]dopamine ([3H]DA), or [3H]ACh were inhibited by 5-OHi. The alpha7nAChR-mediated release of [3H]D-aspartate was reduced by kynurenate at concentrations unable to affect the non-alpha7 receptor-mediated release of tritiated NA, DA or ACh., Conclusions and Implications: (i) 5-hydroxyindole permits selective activation of alpha7nAChRs mediating glutamate release; (ii) kynurenate down-regulates the permissive role of 5-hydroxyindole on alpha7nAChR activation; (iii) the non-alpha7nAChRs mediating release of NA, DA or ACh can be inhibited by 5-hydroxyindole, but not by kynurenate. These findings suggest up the possibility of developing novel drugs able to modulate selectively the cholinergic-glutamatergic transmission.

This article presents a new ab initio force field for the cofactors of bacterial photosynthesis, namely quinones and bacteriochlorophylls. The parameters has been designed to be suitable for molecular dynamics simulations of photosynthetic proteins by being compatible with the AMBER force field. To our knowledge, this is the first force field for photosynthetic cofactors based on a reliable set of ab initio density functional reference data for methyl bacteriochlorophyll a, methyl bacteriopheophytin a, and of a derivative of ubiquinone. Indeed, the new molecular mechanics force field is able to reproduce very well not only the experimental and ab initio structural properties and the vibrational spectra of the molecules, but also the eigenvectors of the molecular normal modes. For this reason it might also be helpful to understand vibrational spectroscopy results obtained on reaction center proteins., (Copyright 2002 Wiley Periodicals, Inc.)

1. The effects of adenosine A2A and A1 receptor activation on the release of glutamate were studied in rat cerebral cortex synaptosomes exposed in superfusion to adenosine receptor ligands. 2. Adenosine (0.1 microM) produced a significant potentiation of the Ca2+-dependent K+ (15 mM)-evoked [3H]-D-aspartate overflow (20.4+/-3.5%), which was blocked by A2A blocker SCH58261 (0.1 microM). At higher concentrations (10 - 1000 microM) adenosine inhibited in a DPCPX-sensitive manner the Ca2+-dependent K+-evoked [3H]-D-aspartate overflow. The inhibitory effect of adenosine at 1000 microM was significantly increased by SCH58261. This inhibition was antagonized by 1 microM DPCPX. Adenosine did not produce any effect on basal release. 3. The A2A receptor agonist CGS 21680 was ineffective on basal release, but stimulated the Ca2+-dependent K+-evoked overflow of [3H]-D-aspartate (EC50 approximately 1 pM). The effect of 0.01 nM CGS 21680 was totally sensitive to the A2A receptor antagonist SCH58261 (IC50 approximately 5 nM). 4. The A1 receptor agonist CCPA inhibited the Ca2+-dependent K+-evoked [3H]-D-aspartate overflow (EC50 approximately 20 nM). The effect of 100 nM CCPA was abolished by 100 nM of the A1 receptor antagonist DPCPX. 5. The K+ (15 mM)-evoked overflow of endogenous glutamate was enhanced by CGS 21680 (0.01 nM) and inhibited by CCPA (0.1 microM). The effect of CGS 21680 was abolished by SCH58261 (0.1 microM) and that of CCPA by DPCPX (0.1 microM). 6. It is concluded that adenosine and adenosine receptor agonists modulate glutamate release by activating inhibitory A1 and excitatory A2A receptors present on glutamatergic terminals of the rat cerebral cortex.

A Non-Parametric Maximum Likelihood approach to the estimation of relative risks in the context of disease mapping is discussed and a NPML approximation to conditional autoregressive models is proposed. NPML estimates have been compared to other proposed solutions (Maximum Likelihood via Monte Carlo Scoring, Hierarchical Bayesian models) using real examples. Overall, the NPML autoregressive estimates (with weighted term) were closer to the Bayesian estimates. The exchangeable NPML model ranked immediately after, even if it implied a greater shrinkage, while the truncated auto-Poisson showed inadequate for disease mapping. The coefficients of the autoregressive term for the different mixtures have clear interpretations: in the breast cancer example, the larger cities in the region showed high rates and very low correlation with the neighbouring areas, while the less populated rural areas with low rates were strongly positively correlated each other. This pattern is expected since breast cancer is strongly correlated with parity and age at first birth, and the female population of the rural areas experienced a decline in fertility much later than those living in the larger cities. The leukemia example highlighted the failure of the Poisson-Gamma model and other general overdispersion tests to detect high risk areas under specific conditions. The NPML approach in Aitkin is very general, simple and flexible. However the user should be warned against the possibility of local maxima and the difficulty in detecting the optimal number of components. Special software (such as CAMAN or DismapWin) had been developed and should be recommended mainly to not experienced users., (Copyright 2000 John Wiley & Sons, Ltd.)

In the present paper a new shrinkage estimator of relative risk, useful in disease mapping, is compared with the empirical and full Bayes estimators, using death certificate data for lung cancer (males and females) and breast cancer (females) 1982-1988 in the Emilia-Romagna region (Italy). The estimates are obtained averaging the relative risks obtained from recursive partitioning of the set of observed values. The number of partitions is fixed in advance and behaves as a smoothing parameter, the lower the number the higher the degree of shrinkage toward the overall mean of the observed values.